The thyroid gland as an intrinsic biologic response-modifier in advanced neoplasia--a novel paradigm

The thyroid gland is the major endocrine modulator of physiological processes crucial to growth, maturation and metabolism. There is, however, a coherent body of evidence suggesting that the thyroid hormones modulate multiple neoplasia-dependent mechanisms. Recently spontaneous remission of metastatic non-small cell carcinoma of lung was reported in a man following recovery from myxedema coma. This rare biological event following a life-threatening clinical syndrome suggests that thyroid hormone deficiency directly or indirectly may significantly alter the balance between malignant tumor viability and growth on the one hand vs. cell death on the other. Evidence, therefore, is presented from clinical and experimental studies suggesting that decreased thyroid function (hypothyroidism) is associated with both enhanced response rates and unusual longevity. Possible mechanisms of action that may promote or retard neoplasia and are dependent on the functional state of the thyroid will be discussed. A novel paradigm is proposed; the thyroid gland aside from its known physiological activity is also the central modulator of solid neoplasia and therefore functions as an intrinsic biologic response-modifier of neoplasia. Induction of a clinically tolerable hypothyroid state in patients could become an integral part of the medical care of advanced cancer in conjunction with standard conventional modalities.